During the past 20 years, bacteria of the Burkholderia cepacia complex (Bcc) have become an important opportunistic pathogen in persons with cystic fibrosis. Patients infected with Bcc exhibit an unpredictable and variable clinical course, with up to 25% developing fatal necrotizing pneumonia. The broad-spectrum antimicrobial resistance of most Bcc strains severely limits treatment options and infection is typically impossible to eradicate. Hence, new strategies are urgently needed to treat Bcc infection in cystic fibrosis patients. Bacteriophages (viruses that specifically detect and kill bacteria) provide a source of antimicrobial activity as yet unexploited in the era of modern biology. Primarily using soil as a source, we have begun assembling and characterizing a library of virulent "killer phages" against Bcc strains. We propose to test the therapeutic effect of phage in a murine lung infection model and an airway epithelial cell culture model. This project will provide critical information about how phage can be used to treat B. cepacia infection in infected individuals. Relevance of this research to public health: Resistance of bacteria to antibiotics continues to increase. This enormous challenge to the treatment of infectious diseases must be met with new strategies to combat infection. One approach, a modern implementation of what was widely used against bacterial infection before the onset of antibiotics, involves the use of naturally occurring 'killer phage", bacterial viruses that are capable of destroying drug-resistant bacteria. This project seeks to explore the use of these natural antibacterial agents to address this critical public health need.